This is an application requesting a state of the art digital transmission electron microscope. Specifically, the funds to purchase a FEI Tecnai 12 Twin Transmission Electron Microscope with a Gatan 794 Multiscan Camera for digital image acquisition are being requested. This state of the art instrument will be incorporated into a Electron Microscopy Core Laboratory for Connective Tissue Research. This will provide access to a group of highly productive and interactive investigators that require access to a high quality transmission electron microscope. The Tecnai 12 transmission electron microscope will support a variety of ongoing research projects, take advantage of available expertise and broaden the scope of structural studies that can be accomplished. The addition of this instrument will facilitate ultrastructural studies at Jefferson generating, in the process, new projects and collaborative interactions. Jefferson Medical College has a large group of established investigators addressing a broad range of questions related to connective tissue biology. Eight major users are identified with research projects addressing: extracellular matrix assembly and connective tissue development; pathology of cutaneous host vs graft disease; biology of proteoglycans in cancer and development; structure and function of extracellular matrix macromolecules/complexes; macromolecular interactions and tissue function; mouse models of cutaneous/connective tissue disease; biology and pathology of the cutaneous basement membrane zone; structure and function of the elastic fiber in development and disease; and development of gene therapy for cutaneous and connective tissue diseases. Each of their research programs would benefit significantly from the availability of a modem, research grade transmission electron microscope.